| First Author | Yap GS | Year | 2001 |
| Journal | J Immunol | Volume | 166 |
| Issue | 9 | Pages | 5720-5 |
| PubMed ID | 11313414 | Mgi Jnum | J:120304 |
| Mgi Id | MGI:3706242 | Doi | 10.4049/jimmunol.166.9.5720 |
| Citation | Yap GS, et al. (2001) A heritable defect in IL-12 signaling in B10.Q/J mice. II. Effect on acute resistance to Toxoplasma gondii and rescue by IL-18 treatment. J Immunol 166(9):5720-5 |
| abstractText | This study documents a defect in IL-12-dependent IFN-gamma responses in a substrain (B10.Q-H2-(q)/SgJ) of B10.Q mice that manifests as an acute susceptibility to infection by the intracellular protozoan pathogen, Toxoplasma gondii. Despite robust systemic production of IL-12, infected B10.Q/J animals fail to mount an early IFN-gamma response after parasite inoculation. Genetic experiments revealed that the host resistance and IFN-gamma production defects are determined by a single autosomal recessive locus distinct from the Stat4 gene. Nonetheless, a delayed IL-12-mediated IFN-gamma response emerges in later stages of acute infection but is unable to prevent host mortality. IL-18 administration restores, in an IL-12-dependent manner, the early IFN-gamma response and host resistance of B10.Q/J animals. These in vivo studies indicate that the partially impaired IL-12 responsiveness in B10.Q/J mice can result in defective host resistance and demonstrate a therapeutic function for IL-18 in reversing a genetically based immunodeficiency in IL-12-dependent IFN-gamma production. |
